This invention relates to devices and methods for controlling ventricular rate during atrial fibrillation, and more particularly to such devices and methods employing nerve stimulation techniques.
Atrial tachycardia, flutter and fibrillation are serious arrhythmias resulting in a low cardiac output and limited exercise tolerance. At present these arrhythmias are treated with drugs, electric shock (cardioversion), or surgical destruction of the atrioventricular (A-V) node and pacemaker implantation. Surgical cutting of atrial tissue to eliminate re-entrant paths is now being investigated. Drug therapy is not always effective and there are undesirable side effects. Although cardioversion abolishes some of these atrial arrhythmias, they usually return because the cause for the arrhythmia is still present. Surgical ablation of the A-V node is successful but leaves the subject with a limited exercise tolerance unless a rate-responsive pacemaker is implanted. These existing approaches are accepted by the medical community and biomedical engineers as the only practical choices, despite the existence of research reported in the literature for years on the subject of electrophysiological techniques involving stimulation of various nerves.
To understand the mechanism of action of an alternative system, proposed herein, for ventricular rate control by means of control of the number of atrial excitations reaching the ventricles, it is useful to review some aspects of the effect of cholinergic drive on the heart. Acetylcholine hyperpolarizes the S-A node and atrial muscle membranes, reduces the refractory period of atrial muscle and weakens the force of atrial contraction. Cholinergic drive also delays or blocks the transmission of excitation across the A-V node.
The cholinergic nerves to the heart are the right and left vagii. The right vagus innervates the S-A node, the atrial muscle and, to a much lesser degree, the A-V node. The left vagus nerve innervates the S-A node and atrial muscle to a lesser degree than it innervates the A-V node. It is well known to physiologists that stimulation of the right vagus nerve predominately slows the S-A node rate and thereby reduces heart rate. Stimulation of the left vagus nerve produces some slowing of the S-A node, prolongation of A-V conduction and partial or total A-V block. We have observed in monophasic atrial electrograms that low-frequency left vagal stimulation causes a dramatic shortening of the duration of the atrial monophasic action potential, indicating shortening of the atrial refractory period. Although the left vagus nerve affects atrial rate to a lesser degree, transmission of excitation across the A-V node is largely regulated by the left vagus nerve.
In atrial fibrillation, the A-V node is bombarded with excitations and responds as rapidly as its refractory period will allow, resulting in rapid, irregular ventricular excitations, i.e., R waves, resulting in varying times for ventricular filling. This results in a rapid, irregular pulse with a pulse deficit. A pulse deficit exists when a ventricular excitation (R wave) does not produce a blood pressure pulse. The mean blood pressure and cardiac output are both reduced as a result of the pulse deficit.
There have been some reports of using electrodes to stimulate the vagus nerve, where such stimulation has an effect on heart rhythm. See, e.g., Bilgutay et al., Vagal Tuning, J. Thoracic Cardiovas. Surg. 56(1):71-82, July, 1968. Bilgutay et al. studied the use of right vagal stimulation for treatment of supraventricular arrhythmias, angina pectoris, and heart failure. Experiments were conducted to determine the effective amplitudes, frequencies, wave shapes and pulse length of the stimulating current to achieve an optimal slowing of the heart rate by stimulating the vagus nerve, the optimal heart rate being defined as the slowest heart rate that could be attained by vagal stimulation without causing A-V dissociation or complete heart block or lowering the ventricular and aortic pressures. The experiments involved the right vagus nerve and resulted in selection of a stimulation amplitude of 6 to 10 volts, a frequency of 10 pulses per second, and 0.2 msec. pulse duration. Voltage increases were noted to decrease heart rate, and a unit triggered by the R waves of the subject's electrocardiogram is described as operating on a servo principle, but apparently in all cases the amplitude and frequency settings are fixed whenever the unit is operating. Bilgutay et al. indicated that the right vagus nerve was stimulated because its distribution is known to be mostly to the sinoatrial node area, but mentioned one experiment in which stimulation of the left vagus slowed the ventricular rate in a dog with complete heart block.
Recognizing the possibility of bradyarrhythmia, one recently proposed approach contemplates the inclusion of cardiac pacing with vagal stimulation. This latter approach to ventricular rate control, which entails a bradyarrhythmia pacemaker, is described in U.S. Pat. No. 5,330,507 to Schwartz. The addition of pacemaker circuitry and related components naturally increases the complexity and cost of the medical device. The patent mentions that stimulation frequency may be varied in a predetermined pattern from an optimum stimulation frequency, amplitude and duration determined during patient workup, if the initial delivered therapy fails to convert the tachyarrhythmia; however, there is no indication of a suitable pattern or any method of implementing it. The device described is designed to generate nerve stimulating pulses having a frequency and amplitude that, while programmable, are fixed once programmed. In essence it is an ON/OFF device that switches state in response to, e.g., the crossing of a heart rate threshold. Such ON/OFF switching, with fixed pulse characteristics, is likely to produce a hunting response, i.e., cycling of the heart rate with episodes of tachycardia. Moreover, although mentioning atrial fibrillation, this patent focuses on prevention or interruption of tachyarrhythmia, and contains no apparent recognition or appreciation that atrial fibrillation can be allowed to persist and that stimulation of the left vagus nerve, as opposed to the right vagus, is necessary and sufficient to effectively control the ventricular rate during atrial fibrillation.
U.S. Pat. No. 5,203,326 to Collins discloses a pacemaker which detects a cardiac abnormality and responds with pacing combined with vagal nerve stimulation. Collins discloses a method of vagal stimulation which includes progressively increasing the stimulation frequency in one-minute intervals and, for the pulse delivery rate selected, slowing the heart rate to a desired, stable level by increasing the pulse current. In the illustrated waveforms (FIGS. 12A-D), there is no correlation between stimulation frequency and ventricular rate. Moreover, the method is open-loop, without regard for the difference between the current rate and a desired rate.
There is also no teaching or suggestion that a simplified device without pacing capability could provide effective control of ventricular rate through vagal stimulation while allowing atrial fibrillation to persist. Furthermore, one of ordinary skill in the art would not read the Collins patent as teaching or suggesting that it is the left vagus nerve that must be stimulated to provide effective control of ventricular rate during atrial fibrillation.
Another device using vagal stimulation for treating tachyarrhythmia is disclosed in a European patent application published in 1995 as Publication No. EP0688577A1. This device is designed to terminate fibrillation by vagal stimulation. There is no disclosure of a method for controlling ventricular rate by vagal stimulation while atrial fibrillation is ongoing and no mention of the use of the left vagus nerve for that purpose.
Thus there remains the need for a system that effectively takes advantage of the phenomenon that transmission across the A-V node is largely, but not entirely, regulated by the left vagus nerve, and, more particularly, provides effective control of electrical stimulation of the vagus nerve to control the number of excitations that reach the ventricles during atrial fibrillation.